Mechanism\nInsight into Direct Amidation Catalyzed\nby Zr Salts: Evidence of Zr Oxo Clusters as Active Species

The capricious reactivity and speciation of earth-abundant\nmetals\n(EAM) hinder the mechanistic understanding essential to boost their\nefficiency and versatility in catalysis. Moreover, metal’s\nsolution chemistry and reactivity are conventionally controlled using\norganic ligands, while their fundamental chemistry in operando conditions\nis often overlooked. However, in this study, we showcase how a better\nunderstanding of in operando conditions may result in improved catalytic\nreactions. By assessing the composition and structure of active species\nfor Zr-catalyzed direct amide bond formations under operating conditions,\nwe discovered zirconium oxo clusters form quickly and are likely active\nspecies in the reactions. Formation of these clusters dismisses the\nuse of additional organic ligands, inert atmosphere, anhydrous solvents,\nor even water scavenging to provide amides in good to excellent yields.\nMore specifically, dodeca- and hexazirconium oxo clusters (Zr<sub>12</sub> and Zr<sub>6</sub>, respectively) rapidly form from commercial,\nreadily available Zr salts under reaction conditions known to afford\namides directly from nonactivated carboxylic acid and amine substrates.\nExtended X-ray absorption fine structure (EXAFS) experiments confirm\nthe presence of oxo clusters in solution throughout the reaction,\nwhile their key role in the mechanism is supported by an in-depth\ncomputational study employing density functional theory (DFT) and\nmolecular dynamics (MD) methods. These results underline the value\nof (earth-abundant) metals’ intrinsic solution chemistry to\ntransformative mechanistic understanding and to enhance the sustainability\nof organic transformations.